We propose to use congenitally athymic (nude) mice infected with the intestinal nematodes, Nippostrongylus brasiliensis and Aspiculuris tetraptera for investigations on the role of humoral and cellular components in helminth immunity. Our previous studies have shown that nude mice are incapable of terminating N. brasiliensis infections, while normal thymus-bearing littermates of nudes, and nudes given thymus gland implants, expel their worm burdens 8-12 days post-larval-inoculation. Antibody, lymphocytes, and a bone marrow-derived cellular component are evidently all required to effect worm expulsion. In addition to the nude mouse, which lacks cell-mediated immunity, we will develop mice totally deficient in humoral immunity (anti-micron-treated normal mice), mice having a combined immunodeficiency (anti-micron-treated nude mice), and lethally irradiated mice. In separate experiments, these hosts will be reconstituted with class-specific immunoglobulins (Ig) derived from immune donors, and with primed lymphocytes (thymus-derived and/or bone marrow-derived) in combination with eosinophils, macrophages or neutrophils from immune mice. Additionally, normal mice, class-specifically immunosuppressed with anti-gamma or anti-alpha serum or treated with antieosinophil serum, will be examined for their ability to expel worms in the absence of individual humoral or cellular components. Mast cell proliferation and IgE production occur during infections of N. brasiliensis. We plan to determine the thymus dependency of both responses by utilizing nude mice. We will also attempt to determine if an IgE-allergen-induced mast cell degranulation is necessary for worm expulsion by immunosuppressing the IgE response and determining worm expulsion. We have observed that the regulation of naturally acquired pinworm burdens, usually considered to be non-immunological, is actually thymus dependent. We plan to develop the A. tetraptera-nude mouse model for studies on host regulation of the equilibrium that exists between host and parasite. BIBLIOGRAPHIC REFERENCE: Jacobson, R.H. and N.D. Reed. 1977. The requirement of thymus competence for both humoral and cell-mediated steps in expulsion of Nippostrongylus brasiliensis from mice. International Archives of Allergy and Applied Immunology - accepted. In press.